Biorhythms of Addiction

Circadian rhythms help the body keep time, but researchers report that they also play a role in forming cocaine habits, at least in fruit flies. The study, reported in today's Science, suggests a new avenue for studying drug addiction.

Give a mouse, man, or any other vertebrate enough doses of a psychostimulant like cocaine, and addiction almost surely will follow. In early 1998, a group led by molecular geneticist Jay Hirsh of the University of Virginia in Charlottesville showed that fruit flies exhibit similar hallmarks of addiction. On a lark, Hirsh's team decided to examine how flies with mutated circadian clocks handle their cocaine.

Hirsh and his colleagues Rozi Andretic and Sarah Chaney administered aerosolized cocaine to fruit flies and watched for signs of a fly high, such as compulsive grooming, proboscis extension, and flying in circles. Normal flies showed preliminary signs of addiction. But flies with mutations in the circadian clock genes called period, clock, cycle, and doubletime never became habituated to the drug, even after repeated exposures.

Next, the researchers gave the flies a single dose of cocaine then monitored the activity of tyrosine decarboxylase (TDC), an enzyme that normally shows a spike in activity after cocaine exposure. TDC activity stayed flat in the mutant flies. That implies that period, clock, cycle, and doubletime are somehow linked to TDC, says Hirsh.

"This is a beautiful little study," says molecular neurobiologist Ron Davis at Baylor College of Medicine in Houston. Up until now, there had only been one noncircadian function--the male's courtship song--linked to these clock genes, says Hirsh. He hopes this study will encourage researchers to take a closer look at the connection between addiction and how the body keeps time.